The high (50-90 percent) mortality of acute intestinal ischemia is due largely to the appearance of irreversible tissue damage prior to therapeutic intervention. This project proposes to investigate those aspects of pathophysiology, diagnosis and treatment that are likely to provide information that is applicable to the management of patients with all forms of ischemic disease of the bowel. Part I will study the basic mechanism of nonocclusive mesenteric ischemia (NOMI) using selective paramacologic blockade of the renin-angiotensin axis and the sympathetic nervous system in a pig model of NOMI produced by pericardial tamponade. We will also evaluate the role of vasospasm in altering collateral flow and thus influencing tissue injury during occlusive mesenteric ischemia in the rat. Part II will investigate mechanisms by which low flow produces intestinal tissue injury. We will evaluate the possible protective role of fructose 1, 6 diphosphate as an anaerobic energy source during bowel ischemia in the rat. In the same model we will study the role of superoxide free radical injury during reperfusion by specific pharmacologic blockade. Finally, we will evaluate the use of fibrinolytic therapy with urokinase to lyse microvascular thrombi, enhance post-ischemic microvascular patency and reperfusion, and thereby improve tissue recovery in rabbits subjected to segmental mesenteric vascular occlusion. Part III will investigate new means for early recognition of intestinal ischemic disease in animals and man. Serum levels of endotoxin, diamine oxidase and the BB isoenzyme of creatinine phosphokinase will be evaluated as indicators of early bowel ischemia in rabbits with segmental vasular occlusion and in patients suspected to have intestinal vascular compromise. In addition, Gamma camera images and activity washout curves obtained following the intraperitoneal administration of 133 Xenon will be evaluated for their ability to detect early low flow states, prior to the development of tissue damage, and to quantitate "effective peritoneal perfusion" as an index of mesenteric blood flow. These studies will be conducted in rats and in patients with suspected ischemic bowel from mesenteric occlusion, NOMI or strangulation obstruction. All our results should be directly applicable to such patients.